|OPIOID-INDUCED CONSTIPATION MANAGEMENT GUIDELINES|
|The management of opioid-induced constipation is based on recommendations from the American Gastroenterological Association (AGA). The guideline only focuses on medical management (both prescription and over-the-counter products) and does not address the role of psychological therapy, alternative medicine approaches, surgery, or devices.|
|ROME IV DIAGNOSTIC CRITERIA|
|Opioid-induced constipation (OIC): new or worsening symptoms of constipation when initiating, changing, or increasing opioid therapy that must include ≥2 of the following (>25% of defecations):
• Lumpy or hard stools
• Sensation of incomplete evacuation
• Sensation of anorectal obstruction or blockage
• Manual maneuvers to facilitate defecations (eg, digital evacuation, support of the pelvic floor)
• Fewer than 3 spontaneous bowel movements per week
|General approach to patients with suspected OIC:
• Ensure that the indication for opioid therapy is appropriate and that the patient is taking the minimum necessary opioid dose.
• Obtain a careful history to evaluate defecation and dietary patterns, stool consistency, symptoms of dyssynergic defecation (eg, sensation of incomplete evacuation), or alarm symptoms (eg, blood in stool or accompanying weight loss).
• Obtain a medical history to assess comorbid illnesses and regular medication use.
• Explore or exclude other potential causes of constipation, such as pelvic outlet dysfunction, mechanical obstruction, metabolic abnormalities, and contributions of other diseases or medications.
|MANAGEMENT OF OIC|
1. Lifestyle modifications (eg, increasing fluid intake, regular moderate exercise, and toileting as soon as possible) are an appropriate first step for all patients with constipation.
2. Changing to an equianalgesic dose of an alternative, less-constipating opioid (“opioid switching”) may be beneficial.
3. Once OIC is confirmed and other causes of constipation excluded, the use of laxatives as first-line agents is recommended.
4. For laxative-refractory1 OIC, it is recommended to use PAMORAs such as naldemedine or naloxegol, and suggested to use methylnaltrexone, over no treatment.
5. No recommendations were made on the use of intestinal secretagogues (lubiprostone) and selective 5-HT agonists (prucalopride) in OIC.
|PHARMACOLOGICAL TREATMENT FOR OIC|
|lactulose||—||10g/15mL||oral soln||15–30mL once daily; max 60mL/day.|
|Kristalose||10g, 20g||crystals for reconstitution||Dissolve 10–20g in 4oz water once daily; max 40g/day.|
|magnesium citrate||—||1.745g/30mL||oral soln||Take with a full 8oz glass of liquid. ≥12yrs: 6.5–10oz (192–296mL) once daily or in divided doses. Max 10oz/24hrs.|
|magnesium hydroxide||—||400mg/5mL||liquid||Take with a full 8oz glass of liquid. ≥12yrs: 30–60mL once daily or in divided doses.|
|polyethylene glycol (PEG)||Glycolax||17g||pwd for oral soln||Dissolve 17g in 8oz water and drink once daily for max 14 days.|
|Miralax||17g||pwd for oral soln||≥17yrs: Dissolve 17g in 4–8oz liquid and drink once daily for max 7 days.|
|bisacodyl||Dulcolax||5mg||e-c tabs||1–3 tabs daily. Results usually within 6–12hrs; reevaluate if ineffective.|
|100mg||softgel||1–3 softgels daily. Results usually within 12–72hrs; reevaluate if ineffective.|
|10mg||supp||1 supp rectally once daily. Retain for 15–20mins. Results usually within 15–60mins; reevaluate if ineffective.|
|Fleet||5mg||tabs||1–3 tabs daily. Results usually within 6–12hrs; reevaluate if ineffective.|
|10mg||supp||1 supp rectally daily. Retain for 15–20mins. Results usually within 15–60mins; reevaluate if ineffective.|
|10mg/30mL||enema||1 enema rectally daily. Results usually within 5–20mins; reevaluate if ineffective.|
|senna||Senokot||8.6mg||tabs||2 tabs once daily; max 4 tabs twice daily.|
|Senokot Xtra||17.2mg||tabs||1 tab once daily; max 2 tabs twice daily.|
|Detergent/surfactant stool softeners|
|docusate sodium||Colace||50mg, 100mg||caps||50–300mg daily.|
|10mg/mL||liquid||Mix in 6–8oz of milk or juice. 50–150mg once or twice daily.|
|60mg/15mL||syrup||Mix in 6–8oz of milk or juice. 60–360mg daily.|
|mineral oil||Fleet Mineral Oil Enema||100%||enema||1 enema rectally daily. Results usually within 2–15mins; reevaluate if ineffective.|
|PERIPHERALLY ACTING μ-OPIOID RECEPTOR ANTAGONISTS (PAMORAs)2|
|methylnaltrexone||Relistor3,4||150mg||tabs||Take on an empty stomach with water ≥30mins before first meal of day. 450mg once daily in the AM. CrCl<60mL/min or hepatic impairment (Child-Pugh B or C): 150mg once daily.|
|8mg/0.4mL, 12mg/0.6mL||soln for SC inj||12mg SC once daily. Advanced illness: give once every other day as needed (max 1 dose/24hrs). <38kg or >114kg: 0.15mg/kg. 38–<62kg: 8mg. 62–114kg: 12mg. Renal (CrCl<60mL/min) or severe hepatic impairment: reduce dose by ½ (see full labeling).|
|naldemedine||Symproic4||0.2mg||tabs||0.2mg once daily.|
|naloxegol||Movantik3,4||12.5mg, 25mg||tabs||Take on an empty stomach. 25mg once daily in the AM; may reduce to 12.5mg once daily if not tolerated. Renal impairment (CrCl<60mL/min): 12.5mg once daily; may increase to 25mg once daily if tolerated.|
|Key:e-c = enteric coated; pwd = powder; soln = solution; supp = suppository.
1 Laxative-refractory OIC is defined as moderate or severe symptoms of constipation despite the use of laxatives from ≥1 laxative classes for a minimum of 4 days within a 2-week period. AGA recommends using a combination of ≥2 types of laxatives before escalating therapy, and that scheduled use of laxatives (vs “as needed” basis) is required before considering alternative treatment.
2 Avoid in conditions that compromise the blood-brain barrier due to potential for serious withdrawal or reversal of anesthesia.
3 Discontinue all laxative therapy prior to initiation; may use as needed if suboptimal response after 3 days.
4 Discontinue if opioid pain therapy is also discontinued.
Not an inclusive list of medications and/or official indications. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.
Adapted from Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2018 Oct 16. pii: S0016-5085(18)34782-6. doi: 10.1053/j.gastro.2018.07.016.